Dengue during pregnancy and adverse fetal outcomes: a systematic review and meta-analysis. 2016

Enny S Paixão, and Maria Gloria Teixeira, and Maria da Conceição N Costa, and Laura C Rodrigues
Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: enny.cruz@lshtm.ac.uk.

BACKGROUND Little is known about the possible adverse effects of dengue infection during pregnancy on fetal outcomes. In this systematic review and meta-analysis we aimed to estimate the increase in risk of four adverse fetal outcomes in women who had dengue infection during pregnancy. METHODS For this systematic review and meta-analysis, we searched Medline, Embase, Global Health Library, and Scopus for articles published before Aug 1, 2015. We included original studies that reported any fetal outcomes for pregnant women who had dengue infection during the gestational period. Case-control, cohort, and cross-sectional studies and unselected case series were eligible for inclusion. We excluded case reports, ecological studies, reviews, in-vitro studies, and studies without data for pregnancy outcomes. We independently screened titles and abstracts to select papers for inclusion and scored the quality of those included in meta-analyses. For each study, we recorded study design, year of publication, study location, period of study, and authors and we extracted data for population characteristics such as the number of pregnancies, dengue diagnostic information, and the frequency of outcomes. We investigated four adverse fetal outcomes: stillbirth, miscarriage, preterm birth, and low birthweight. We estimated the increase in risk of these adverse fetal outcomes by use of Mantel-Haenszel methods. We assessed heterogeneity of odds ratios (OR) with the I(2) statistic. RESULTS We identified 278 non-duplicate records, of which 107 full-text articles were screened for eligibility. 16 studies were eligible for inclusion in the systematic review and eight were eligible for the meta-analyses, which included 6071 pregnant women, 292 of whom were exposed to dengue during pregnancy. For miscarriage, the OR was 3·51 (95% CI 1·15-10·77, I(2)=0·0%, p=0·765) for women with dengue infection during pregnancy compared with those without. We did not do a meta-analysis for stillbirth because this outcome was investigated in only one study with a comparison group; we calculated the crude relative risk to be 6·7 (95% CI 2·1-21·3) in women with symptomatic dengue compared with women without dengue. Preterm birth and low birthweight were the most common adverse pregnancy outcomes. The OR for the association with dengue was 1·71 (95% CI 1·06-2·76, I(2)=56·1%, p=0·058) for preterm birth and 1·41 (95% CI 0·90-2·21, I(2)=0·0%, p=0·543) for low birthweight. CONCLUSIONS Evidence suggests that symptomatic dengue during pregnancy might be associated with fetal adverse outcomes. If confirmed, it would be important to monitor pregnancies during which dengue is diagnosed and to consider pregnant women in dengue control policies. BACKGROUND National Council for Scientific and Technological Development (CNPq).

UI MeSH Term Description Entries
D007230 Infant, Low Birth Weight An infant having a birth weight of 2500 gm. (5.5 lb.) or less but INFANT, VERY LOW BIRTH WEIGHT is available for infants having a birth weight of 1500 grams (3.3 lb.) or less. Low Birth Weight,Low-Birth-Weight Infant,Birth Weight, Low,Birth Weights, Low,Infant, Low-Birth-Weight,Infants, Low-Birth-Weight,Low Birth Weight Infant,Low Birth Weights,Low-Birth-Weight Infants
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011251 Pregnancy Complications, Infectious The co-occurrence of pregnancy and an INFECTION. The infection may precede or follow FERTILIZATION. Complications, Infectious Pregnancy,Infectious Pregnancy Complications,Maternal Sepsis,Pregnancy, Infectious Complications,Sepsis during Pregnancy,Sepsis in Pregnancy,Infectious Pregnancy Complication,Pregnancy Complication, Infectious,Sepsis in Pregnancies,Sepsis, Maternal
D011256 Pregnancy Outcome Results of conception and ensuing pregnancy, including LIVE BIRTH; STILLBIRTH; or SPONTANEOUS ABORTION. The outcome may follow natural or artificial insemination or any of the various ASSISTED REPRODUCTIVE TECHNIQUES, such as EMBRYO TRANSFER or FERTILIZATION IN VITRO. Outcome, Pregnancy,Outcomes, Pregnancy,Pregnancy Outcomes
D003430 Cross-Sectional Studies Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time. Disease Frequency Surveys,Prevalence Studies,Analysis, Cross-Sectional,Cross Sectional Analysis,Cross-Sectional Survey,Surveys, Disease Frequency,Analyses, Cross Sectional,Analyses, Cross-Sectional,Analysis, Cross Sectional,Cross Sectional Analyses,Cross Sectional Studies,Cross Sectional Survey,Cross-Sectional Analyses,Cross-Sectional Analysis,Cross-Sectional Study,Cross-Sectional Surveys,Disease Frequency Survey,Prevalence Study,Studies, Cross-Sectional,Studies, Prevalence,Study, Cross-Sectional,Study, Prevalence,Survey, Cross-Sectional,Survey, Disease Frequency,Surveys, Cross-Sectional
D003715 Dengue An acute febrile disease transmitted by the bite of AEDES mosquitoes infected with DENGUE VIRUS. It is self-limiting and characterized by fever, myalgia, headache, and rash. SEVERE DENGUE is a more virulent form of dengue. Dengue Fever,Break-Bone Fever,Breakbone Fever,Classical Dengue,Classical Dengue Fever,Break Bone Fever,Classical Dengue Fevers,Classical Dengues,Dengue Fever, Classical,Dengue, Classical,Fever, Break-Bone,Fever, Breakbone,Fever, Dengue
D005260 Female Females
D005333 Fetus The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN. Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012306 Risk The probability that an event will occur. It encompasses a variety of measures of the probability of a generally unfavorable outcome. Relative Risk,Relative Risks,Risk, Relative,Risks,Risks, Relative

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